Drugs such as cocaine, the opiates and nicotine lose much of their effectiveness--that is, show tolerance--after repeated administration. It was once thought that the development of drug tolerance depended exclusively only on exposure to the drug. However, it is now quite clear that learned associations with the environmental conditions within which drugs are taken, referred to as drug-related cues, can greatly influence this tolerance process. Dr. Caggiula and his colleagues have recently demonstrated that tolerance to both the analgesic and appetite- suppressant effects of nicotine are strongly influenced by learned associations with environmental cues signaling drug delivery. Administering the drug in the absence of these cues reverses the tolerance, and, renders the drug significantly more effective. Dr. Caggiula is now extending and complementing this work with more detailed learning analyses. The first series of studies focuses on pharmacological and learning variables that control the maintenance of tolerance, using rats that had previously been made tolerant to the anorectic effects of nicotine. The second series of experiments are investigating which factors that are responsible for the development of tolerance in drug-naive rats.
